HU201063B - Process for producing enolether derivatives of piroxicames - Google Patents

Process for producing enolether derivatives of piroxicames Download PDF

Info

Publication number: HU201063B
Authority: HU; Hungary
Prior art keywords: mmol; methyl; found; formula; nmr
Prior art date: 1983-12-21

Application number

HU844756A

Other languages

English (en)

Hungarian (hu)

Other versions

HUT37426A (en

Inventor

Anthony Marfat

Original Assignee

Pfizer

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1983-12-21

Filing date

1984-12-20

Publication date

1990-09-28

1984-12-20 Application filed by Pfizer filed Critical Pfizer

1985-12-28 Publication of HUT37426A publication Critical patent/HUT37426A/hu

1990-09-28 Publication of HU201063B publication Critical patent/HU201063B/hu

Links

238000000034 method Methods 0.000 title claims description 31
150000002084 enol ethers Chemical class 0.000 title abstract description 5
150000001875 compounds Chemical class 0.000 claims abstract description 27
238000002360 preparation method Methods 0.000 claims description 14
239000000463 material Substances 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
125000000217 alkyl group Chemical group 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
239000001257 hydrogen Substances 0.000 claims description 2
229910052739 hydrogen Inorganic materials 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
239000007858 starting material Substances 0.000 claims description 2
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
125000005843 halogen group Chemical group 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
230000000269 nucleophilic effect Effects 0.000 claims 1
UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims 1
230000003110 anti-inflammatory effect Effects 0.000 abstract description 6
229940111133 antiinflammatory and antirheumatic drug oxicams Drugs 0.000 abstract description 6
229940002612 prodrug Drugs 0.000 abstract description 6
239000000651 prodrug Substances 0.000 abstract description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
239000000047 product Substances 0.000 description 57
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 56
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 53
238000005160 1H NMR spectroscopy Methods 0.000 description 48
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 40
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
-1 enol esters Chemical class 0.000 description 34
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 34
238000004458 analytical method Methods 0.000 description 31
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 30
QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 30
239000007787 solid Substances 0.000 description 30
229960002702 piroxicam Drugs 0.000 description 29
239000003921 oil Substances 0.000 description 28
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 27
238000004587 chromatography analysis Methods 0.000 description 25
238000001819 mass spectrum Methods 0.000 description 25
238000010992 reflux Methods 0.000 description 23
239000013078 crystal Substances 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 19
239000011541 reaction mixture Substances 0.000 description 19
239000003480 eluent Substances 0.000 description 18
229910000027 potassium carbonate Inorganic materials 0.000 description 17
235000011181 potassium carbonates Nutrition 0.000 description 16
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 15
229910052757 nitrogen Inorganic materials 0.000 description 15
239000000741 silica gel Substances 0.000 description 15
229910002027 silica gel Inorganic materials 0.000 description 15
239000006260 foam Substances 0.000 description 12
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
229910052938 sodium sulfate Inorganic materials 0.000 description 11
235000011152 sodium sulphate Nutrition 0.000 description 11
238000006243 chemical reaction Methods 0.000 description 10
239000012044 organic layer Substances 0.000 description 10
239000012267 brine Substances 0.000 description 9
235000009518 sodium iodide Nutrition 0.000 description 9
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
238000005481 NMR spectroscopy Methods 0.000 description 8
239000010410 layer Substances 0.000 description 8
238000004809 thin layer chromatography Methods 0.000 description 8
238000001953 recrystallisation Methods 0.000 description 6
239000000126 substance Substances 0.000 description 6
239000012074 organic phase Substances 0.000 description 5
239000000243 solution Substances 0.000 description 5
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
JRCUJOMLYAQHDP-UHFFFAOYSA-N chloromethyl octanoate Chemical compound CCCCCCCC(=O)OCCl JRCUJOMLYAQHDP-UHFFFAOYSA-N 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
239000000203 mixture Substances 0.000 description 4
CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 4
NIGKHKLDZOHYMT-UHFFFAOYSA-N 4-hydroxy-2-methyl-n-(6-methylpyridin-2-yl)-1,1-dioxo-1$l^{6},2-benzothiazine-3-carboxamide Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC(C)=N1 NIGKHKLDZOHYMT-UHFFFAOYSA-N 0.000 description 3
WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
FRPHFZCDPYBUAU-UHFFFAOYSA-N Bromocresolgreen Chemical compound CC1=C(Br)C(O)=C(Br)C=C1C1(C=2C(=C(Br)C(O)=C(Br)C=2)C)C2=CC=CC=C2S(=O)(=O)O1 FRPHFZCDPYBUAU-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
BOXZXICVMMSYPE-UHFFFAOYSA-N chloromethyl benzoate Chemical compound ClCOC(=O)C1=CC=CC=C1 BOXZXICVMMSYPE-UHFFFAOYSA-N 0.000 description 3
BDPZFQLKFUONAG-UHFFFAOYSA-N chloromethyl butanoate Chemical compound CCCC(=O)OCCl BDPZFQLKFUONAG-UHFFFAOYSA-N 0.000 description 3
JUBQFNSRJOLWED-UHFFFAOYSA-N chloromethyl heptanoate Chemical compound CCCCCCC(=O)OCCl JUBQFNSRJOLWED-UHFFFAOYSA-N 0.000 description 3
239000012230 colorless oil Substances 0.000 description 3
239000000284 extract Substances 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 2
239000002260 anti-inflammatory agent Substances 0.000 description 2
229940124599 anti-inflammatory drug Drugs 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
DFFDSQBEGQFJJU-UHFFFAOYSA-M butyl carbonate Chemical compound CCCCOC([O-])=O DFFDSQBEGQFJJU-UHFFFAOYSA-M 0.000 description 2
KBPLFHHGFOOTCA-UHFFFAOYSA-N caprylic alcohol Natural products CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
239000002178 crystalline material Substances 0.000 description 2
MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 2
238000001514 detection method Methods 0.000 description 2
238000004821 distillation Methods 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000003814 drug Substances 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
GECNIOWBEXHZNM-UHFFFAOYSA-N hexyl hydrogen carbonate Chemical compound CCCCCCOC(O)=O GECNIOWBEXHZNM-UHFFFAOYSA-N 0.000 description 2
SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
YYUAYBYLJSNDCX-UHFFFAOYSA-N isoxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC=1C=C(C)ON=1 YYUAYBYLJSNDCX-UHFFFAOYSA-N 0.000 description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
CXHHBNMLPJOKQD-UHFFFAOYSA-M methyl carbonate Chemical compound COC([O-])=O CXHHBNMLPJOKQD-UHFFFAOYSA-M 0.000 description 2
RZKVHIPRDKHSAJ-UHFFFAOYSA-N octyl hydrogen carbonate Chemical compound CCCCCCCCOC(O)=O RZKVHIPRDKHSAJ-UHFFFAOYSA-N 0.000 description 2
AHIHJODVQGBOND-UHFFFAOYSA-M propan-2-yl carbonate Chemical compound CC(C)OC([O-])=O AHIHJODVQGBOND-UHFFFAOYSA-M 0.000 description 2
FOWDZVNRQHPXDO-UHFFFAOYSA-N propyl hydrogen carbonate Chemical compound CCCOC(O)=O FOWDZVNRQHPXDO-UHFFFAOYSA-N 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
239000008259 solid foam Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
JUDCUDVGMISCLV-UHFFFAOYSA-N 1-[[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxy]ethyl 2-methylpropanoate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OC(OC(=O)C(C)C)C)=C1C(=O)NC1=CC=CC=N1 JUDCUDVGMISCLV-UHFFFAOYSA-N 0.000 description 1
HJWMJHXNDBVWHP-UHFFFAOYSA-N 1-[[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxy]ethyl octanoate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OC(C)OC(=O)CCCCCCC)=C1C(=O)NC1=CC=CC=N1 HJWMJHXNDBVWHP-UHFFFAOYSA-N 0.000 description 1
USBMASWLIWZNPT-UHFFFAOYSA-N 1-[[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1$l^{6},2-benzothiazin-4-yl]oxy]ethyl propan-2-yl carbonate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OC(C)OC(=O)OC(C)C)=C1C(=O)NC1=CC=CC=N1 USBMASWLIWZNPT-UHFFFAOYSA-N 0.000 description 1
RJVLZFDMDSHJIY-UHFFFAOYSA-N 1-[[2-methyl-1,1-dioxo-3-(pyridin-2-ylcarbamoyl)-1lambda6,2-benzothiazin-4-yl]oxy]ethyl propanoate Chemical compound CN1S(=O)(=O)C2=CC=CC=C2C(OC(C)OC(=O)CC)=C1C(=O)NC1=CC=CC=N1 RJVLZFDMDSHJIY-UHFFFAOYSA-N 0.000 description 1
LIKMAJRDDDTEIG-UHFFFAOYSA-N 1-hexene Chemical compound CCCCC=C LIKMAJRDDDTEIG-UHFFFAOYSA-N 0.000 description 1
YJLUBHOZZTYQIP-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=N2 YJLUBHOZZTYQIP-UHFFFAOYSA-N 0.000 description 1
ODQLAECNMKXOBI-UHFFFAOYSA-N 2-bromo-2h-furan-5-one Chemical compound BrC1OC(=O)C=C1 ODQLAECNMKXOBI-UHFFFAOYSA-N 0.000 description 1
SEEYHRCMNMPHDG-UHFFFAOYSA-N 2-chloroethyl ethyl carbonate Chemical compound CCOC(=O)OCCCl SEEYHRCMNMPHDG-UHFFFAOYSA-N 0.000 description 1
DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 1
FHYFLMZUZUUPDY-UHFFFAOYSA-N 2h-thiazine-3-carboxamide Chemical class NC(=O)C1=CC=CSN1 FHYFLMZUZUUPDY-UHFFFAOYSA-N 0.000 description 1
CLMSHAWYULIVFQ-UHFFFAOYSA-N 3-bromo-3h-2-benzofuran-1-one Chemical compound C1=CC=C2C(Br)OC(=O)C2=C1 CLMSHAWYULIVFQ-UHFFFAOYSA-N 0.000 description 1
KUSPKTGYJLPTSN-UHFFFAOYSA-N 3-nitro-n-[3-[(1-oxo-3h-2-benzofuran-5-yl)amino]quinoxalin-2-yl]benzenesulfonamide Chemical compound [O-][N+](=O)C1=CC=CC(S(=O)(=O)NC=2C(=NC3=CC=CC=C3N=2)NC=2C=C3COC(=O)C3=CC=2)=C1 KUSPKTGYJLPTSN-UHFFFAOYSA-N 0.000 description 1
GWFALVUXAGYMHR-UHFFFAOYSA-N 4-(bromomethyl)-5-methyl-1,3-dioxol-2-one Chemical compound CC=1OC(=O)OC=1CBr GWFALVUXAGYMHR-UHFFFAOYSA-N 0.000 description 1
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
208000009386 Experimental Arthritis Diseases 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
206010030124 Oedema peripheral Diseases 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
229940121363 anti-inflammatory agent Drugs 0.000 description 1
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
230000002051 biphasic effect Effects 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229940045348 brown mixture Drugs 0.000 description 1
DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
PJGJQVRXEUVAFT-UHFFFAOYSA-N chloroiodomethane Chemical compound ClCI PJGJQVRXEUVAFT-UHFFFAOYSA-N 0.000 description 1
GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 1
HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
FRJZOYQRAJDROR-UHFFFAOYSA-N cyclohexyl hydrogen carbonate Chemical compound OC(=O)OC1CCCCC1 FRJZOYQRAJDROR-UHFFFAOYSA-N 0.000 description 1
ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
239000013583 drug formulation Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
238000005187 foaming Methods 0.000 description 1
230000005021 gait Effects 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
239000008241 heterogeneous mixture Substances 0.000 description 1
RBBOWEDMXHTEPA-UHFFFAOYSA-N hexane;toluene Chemical compound CCCCCC.CC1=CC=CC=C1 RBBOWEDMXHTEPA-UHFFFAOYSA-N 0.000 description 1
YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 description 1
125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
ZUBZATZOEPUUQF-UHFFFAOYSA-N isopropylhexane Natural products CCCCCCC(C)C ZUBZATZOEPUUQF-UHFFFAOYSA-N 0.000 description 1
229950002252 isoxicam Drugs 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
230000037353 metabolic pathway Effects 0.000 description 1
229940050176 methyl chloride Drugs 0.000 description 1
ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
TVMXDCGIABBOFY-UHFFFAOYSA-N n-Octanol Natural products CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
238000007344 nucleophilic reaction Methods 0.000 description 1
238000010534 nucleophilic substitution reaction Methods 0.000 description 1
WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
REEZZSHJLXOIHL-UHFFFAOYSA-N octanoyl chloride Chemical compound CCCCCCCC(Cl)=O REEZZSHJLXOIHL-UHFFFAOYSA-N 0.000 description 1
125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
230000001568 sexual effect Effects 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
MFBOGIVSZKQAPD-UHFFFAOYSA-M sodium butyrate Chemical compound [Na+].CCCC([O-])=O MFBOGIVSZKQAPD-UHFFFAOYSA-M 0.000 description 1
BYKRNSHANADUFY-UHFFFAOYSA-M sodium octanoate Chemical compound [Na+].CCCCCCCC([O-])=O BYKRNSHANADUFY-UHFFFAOYSA-M 0.000 description 1
NMTDPTPUELYEPL-UHFFFAOYSA-M sodium;heptanoate Chemical compound [Na+].CCCCCCC([O-])=O NMTDPTPUELYEPL-UHFFFAOYSA-M 0.000 description 1
239000002904 solvent Substances 0.000 description 1
238000005507 spraying Methods 0.000 description 1
LZNWYQJJBLGYLT-UHFFFAOYSA-N tenoxicam Chemical compound OC=1C=2SC=CC=2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 LZNWYQJJBLGYLT-UHFFFAOYSA-N 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
125000005490 tosylate group Chemical group 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C68/00—Preparation of esters of carbonic or haloformic acids
- C07C68/02—Preparation of esters of carbonic or haloformic acids from phosgene or haloformates
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Plural Heterocyclic Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Steroid Compounds (AREA)

HU844756A 1983-12-21 1984-12-20 Process for producing enolether derivatives of piroxicames HU201063B (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US56390283A	1983-12-21	1983-12-21
US06/606,113 US4551452A (en)	1983-12-21	1984-05-02	Anti-inflammatory 2-methyl-2H-1,2-benzo-(or -thieno-)thiazine-3-carboxamide 1,1-dioxide derivatives, compositions, and method of use therefor

Publications (2)

Publication Number	Publication Date
HUT37426A HUT37426A (en)	1985-12-28
HU201063B true HU201063B (en)	1990-09-28

Family

ID=27073413

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HU844756A HU201063B (en)	1983-12-21	1984-12-20	Process for producing enolether derivatives of piroxicames

Country Status (26)

Country	Link
US (1)	US4551452A (fr)
EP (1)	EP0147177B1 (fr)
KR (1)	KR860002035B1 (fr)
AU (1)	AU552940B2 (fr)
BG (1)	BG47946A3 (fr)
CA (1)	CA1255302A (fr)
DD (1)	DD229125A5 (fr)
DE (1)	DE3466776D1 (fr)
DK (1)	DK166678B1 (fr)
EG (1)	EG17049A (fr)
ES (1)	ES8604215A1 (fr)
FI (1)	FI79850C (fr)
GR (1)	GR82512B (fr)
HK (1)	HK58589A (fr)
HU (1)	HU201063B (fr)
IE (1)	IE57680B1 (fr)
IL (1)	IL73873A (fr)
MX (2)	MX174596B (fr)
NO (1)	NO161317C (fr)
NZ (1)	NZ210632A (fr)
PH (1)	PH21447A (fr)
PL (1)	PL145989B1 (fr)
PT (1)	PT79700B (fr)
RO (1)	RO90048A (fr)
SG (1)	SG27001G (fr)
YU (1)	YU43677B (fr)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4906635A (en) *	1983-11-25	1990-03-06	Schering Corporation	Carboxyalkyl dipeptides as antiglaucoma agents
US5017567A (en) *	1983-11-25	1991-05-21	Schering Corporation	Carboxyalkyl dipeptides as antiglaucoma agents
US4616012A (en) *	1983-11-25	1986-10-07	Schering Corporation	Carboxyalkyl dipeptides as antiglaucoma agents
US4778795A (en) *	1983-11-25	1988-10-18	Schering Corporation	Carboxyalkyl dipeptides as antiglaucoma agents
US4623486A (en) *	1985-05-29	1986-11-18	Pfizer Inc.	[4-substituted benzoyloxy]-N-substituted-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxides having anti-arthritic activity
KR890001236B1 (ko) *	1985-10-02	1989-04-28	화이자 인코포레이티드	소염제 조성물의 제조방법
US4771071A (en) *	1986-05-05	1988-09-13	Merck & Co., Inc.	Antihypercholesterolemic compounds
US4829062A (en) *	1986-05-16	1989-05-09	Pfizer Inc.	Benzothiazine dioxide derivatives
US5081118A (en) *	1987-10-26	1992-01-14	Pfizer Inc.	Benzothiazine dioxide derivatives
IL87951A (en) *	1987-10-29	1992-03-29	Chem Pharm Forsch Gmbh	Carbonic acid esters of 6-chloro-4-(1-hydroxyethoxy)-2-methyl-n-(2-pyridyl)-2h-thieno(2,3-e)-1,2-thiazine-3-carboxamide 1,1-dioxide,their preparation and pharmaceutical compositions containing them
ZA945190B (en) *	1993-07-30	1995-02-24	Kotobuki Seiyaku Co Ltd	Carboxymethylidenecycloheptimidazole derivatives method or manufacturing the same and therapeutic agents containing these compounds
IT1308633B1 (it)	1999-03-02	2002-01-09	Nicox Sa	Nitrossiderivati.
CN100389114C (zh) *	2006-01-17	2008-05-21	南京新港医药有限公司	一种安吡昔康的精制方法
US20090238763A1 (en) *	2006-07-09	2009-09-24	Chongxi Yu	High penetration compositions and uses thereof
US20090221703A1 (en)	2006-07-09	2009-09-03	Chongxi Yu	High penetration composition and uses thereof
EP2084165B1 (fr) *	2006-10-11	2013-06-12	Techfields Biochem Co. Ltd	Pro-médicaments d'oxicams solubles dans l'eau et chargés positivement et composés apparentés avec une vitesse de pénétration de la peau très élevée
JP2010529101A (ja) *	2007-06-04	2010-08-26	テックフィールズインコーポレイテッド	非常に速い皮膚及び膜浸透速度を有するｎｓａｉａプロドラッグ及びその新規医薬使用
CN108191846B (zh)	2008-12-04	2021-08-20	于崇曦	高穿透性组合物及其应用
WO2013093931A2 (fr)	2011-09-19	2013-06-27	Sun Pharma Advanced Research Company Ltd.	Nouveaux promédicaments de médicaments phénoliques

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3591584A (en) *	1968-08-27	1971-07-06	Pfizer	Benzothiazine dioxides
US3787324A (en) *	1971-03-01	1974-01-22	Warner Lambert Co	4-hydroxy-3-(3-isoxazolocarbamyl)-2h-1,2-benzothiazine 1,dioxides and process for their production
US3892740A (en) *	1974-10-15	1975-07-01	Pfizer	Process for the production of carboxamides of oxo-1,2-benzothiazine-1,1-dioxides
AU518216B2 (en) *	1977-09-06	1981-09-17	Hafslund Nycomed Pharma Aktiengesellschaft	Thienothiazine derivatives
US4309427A (en) *	1981-01-15	1982-01-05	Pfizer Inc.	Benzothiazine dioxide derivatives
IT1168064B (it) *	1981-11-12	1987-05-20	Prodotti Antibiotici Spa	Composto ad azione antinfiammatoria
IT8219486A0 (it) *	1982-02-05	1982-02-05	Chiesi Farma Spa	Nuovi composti ad attivita'antiinfiammatoria, procedimento per la loro preparazione e relative composizioni farmaceutiche.

1984
- 1984-05-02 US US06/606,113 patent/US4551452A/en not_active Expired - Lifetime
- 1984-11-28 PH PH31504A patent/PH21447A/en unknown
- 1984-12-18 PT PT79700A patent/PT79700B/pt unknown
- 1984-12-19 RO RO84116745A patent/RO90048A/fr unknown
- 1984-12-19 SG SG305/89A patent/SG27001G/en unknown
- 1984-12-19 NZ NZ210632A patent/NZ210632A/en unknown
- 1984-12-19 EG EG786/84A patent/EG17049A/xx active
- 1984-12-19 CA CA000470471A patent/CA1255302A/fr not_active Expired
- 1984-12-19 GR GR82512A patent/GR82512B/el unknown
- 1984-12-19 IE IE3260/84A patent/IE57680B1/en not_active IP Right Cessation
- 1984-12-19 DE DE8484308926T patent/DE3466776D1/de not_active Expired
- 1984-12-19 PL PL1984251040A patent/PL145989B1/pl unknown
- 1984-12-19 EP EP84308926A patent/EP0147177B1/fr not_active Expired
- 1984-12-20 AU AU36997/84A patent/AU552940B2/en not_active Expired
- 1984-12-20 FI FI845074A patent/FI79850C/fi active IP Right Grant
- 1984-12-20 BG BG067990A patent/BG47946A3/xx unknown
- 1984-12-20 DD DD84271297A patent/DD229125A5/de not_active IP Right Cessation
- 1984-12-20 YU YU2160/84A patent/YU43677B/xx unknown
- 1984-12-20 MX MX005836A patent/MX174596B/es unknown
- 1984-12-20 ES ES538907A patent/ES8604215A1/es not_active Expired
- 1984-12-20 KR KR1019840008144A patent/KR860002035B1/ko not_active Expired
- 1984-12-20 NO NO845145A patent/NO161317C/no not_active IP Right Cessation
- 1984-12-20 HU HU844756A patent/HU201063B/hu unknown
- 1984-12-20 DK DK614984A patent/DK166678B1/da active
- 1984-12-20 IL IL73873A patent/IL73873A/xx not_active IP Right Cessation
1989
- 1989-07-20 HK HK585/89A patent/HK58589A/en not_active IP Right Cessation
1992
- 1992-06-29 MX MX9203740A patent/MX9203740A/es unknown

Also Published As

Publication number	Publication date
DK166678B1 (da)	1993-06-28
EP0147177A3 (en)	1985-08-14
AU3699784A (en)	1985-07-04
BG47946A3 (en)	1990-10-15
NO845145L (no)	1985-06-24
DK614984A (da)	1985-07-17
DD229125A5 (de)	1985-10-30
HUT37426A (en)	1985-12-28
ES8604215A1 (es)	1986-01-16
CA1255302A (fr)	1989-06-06
NZ210632A (en)	1987-02-20
FI79850C (fi)	1990-03-12
EP0147177B1 (fr)	1987-10-14
IL73873A (en)	1988-02-29
GR82512B (en)	1985-04-22
PL251040A1 (en)	1985-10-22
EP0147177A2 (fr)	1985-07-03
FI79850B (fi)	1989-11-30
PT79700B (en)	1986-12-30
YU216084A (en)	1986-10-31
PH21447A (en)	1987-10-28
SG27001G (en)	1989-08-11
DK614984D0 (da)	1984-12-20
US4551452A (en)	1985-11-05
ES538907A0 (es)	1986-01-16
HK58589A (en)	1989-07-28
FI845074A0 (fi)	1984-12-20
MX174596B (es)	1994-05-30
RO90048A (fr)	1986-09-30
DE3466776D1 (en)	1987-11-19
MX9203740A (es)	1992-09-01
KR860002035B1 (ko)	1986-11-17
KR850004492A (ko)	1985-07-15
EG17049A (en)	1991-03-30
YU43677B (en)	1989-10-31
IL73873A0 (en)	1985-03-31
IE843260L (en)	1985-06-21
NO161317B (no)	1989-04-24
NO161317C (no)	1989-08-02
IE57680B1 (en)	1993-02-24
FI845074L (fi)	1985-06-22
PL145989B1 (en)	1988-12-31
PT79700A (en)	1985-01-01
AU552940B2 (en)	1986-06-26

Publication	Publication Date	Title
EP0147177B1 (fr)	1987-10-14	Promédicaments éthers d'oxicames anti-inflammatoires
JP5305914B2 (ja)	2013-10-02	オキサゾール化合物及び医薬組成物
HU219950B (hu)	2001-09-28	Proteolitikus enzimeket gátló szacharinszármazékok és ezeket tartalmazó gyógyászati készítmények, valamint a szacharinszármazékok előállítása
PT98292A (pt)	1992-05-29	Processo para a preparacao de heterociclos tioxo e de composicoes farmaceuticas que os contem
HU217907B (hu)	2000-05-28	Kinolin- vagy kinazolinszármazékok, eljárás a vegyületek előállítására és a vegyületeket tartalmazó gyógyászati készítmények
NL8800465A (nl)	1988-09-16	Antihypercholesterolemische tetrazoolverbindingen.
IE75733B1 (en)	1997-09-24	Benzene pyridine and pyrimidine derivative
JP4986927B2 (ja)	2012-07-25	医薬
KR850000923B1 (ko)	1985-06-28	피록시캄의 제조 방법
JPS6159313B2 (fr)	1986-12-16
CZ280695A3 (en)	1996-01-17	Ether derivatives, process of their preparation and pharmaceutical compositions containing thereof
FR2496106A1 (fr)	1982-06-18	Derives d'acide 7-acylaminocephalosporanique et procede pour leur preparation
EP0191045B1 (fr)	1989-12-20	Utilisation des derives de l'acide 4-(isoxazolyl)-thiazole-2-oxamique
JPH044312B2 (fr)	1992-01-27
CA1157864A (fr)	1983-11-29	Thiazoles triaryliques substitues
KR890002291B1 (ko)	1989-06-28	2-알킬벤즈이미다졸 유도체의 제조방법
EP0142754A2 (fr)	1985-05-29	Acides benzoiques substitués sur la position 2, ayant un groupe imidazolyl, procédé pour leur préparation et compositions pharmaceutiques les contenant
JPH07103105B2 (ja)	1995-11-08	インドール誘導体及びその製造方法
CS248726B2 (cs)	1987-02-12	Způsob výroby etherových prekursorů protizánětlivě účinných oxicamů
HU201532B (en)	1990-11-28	Process for producing intermediates for the purpose of obtaining tetrazole derivatives reducing pathologically high cholesterin level of blood
HUT69689A (en)	1995-09-28	Prodrugs of antiinflammatory 3-acyl-2-oxindole-1-carboxamides, pharmaceutical compositions containing them, and process for their preparation
JPH08325265A (ja)	1996-12-10	チアゾリルベンゾフラン誘導体の製造方法、および該製造方法に用いられる化合物
JPH0125742B2 (fr)	1989-05-19
JPH0121143B2 (fr)	1989-04-19
JPH08505865A (ja)	1996-06-25	オキシム誘導体